Preventive effects of intrauterine injection of bone marrow-derived mesenchymal stem cell-conditioned media on uterine fibrosis immediately after endometrial curettage in rabbit

Abstract

Background Uterine fibrosis is a uterine acquired disorder with symptoms of implantation disturbances, menstrual irregularities and abortion. Mesenchymal stem cells (MSCs) have antifibrotic properties by secretion of chemokines. MSCs-conditioned media (MSC-CM) contains paracrine components, exosomes, with a great potential for repairing damaged tissue or prevention of fibrosis. The main goal of this study was to evaluate the preventive effects of bone marrow-derived MSC-CM (BM-MSC-CM) on uterine fibrosis after uterine curettage in rabbits. Methods This study included 12 female rabbits (24 uterine horns) that double uteri of each 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSCs injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were assigned in different groups. The MSC-CM was collected from cultivated BM-MSCs 48 h after three times washing and replacement of serum free media. Through a surgical approach, except intact negative uteri, the caudal part of the uteri was submitted traumatic endometrial curettage. After suturing of uterine wall, BM-MSC or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Results Curettage with or without preventive injections increased the growth of endometrial layer based on the histomorphometric indices evaluation. However, the amount of fibrotic tissue in the BM-MSC-CM injection group was lower than the BM-MSC and the curettage group, single injection of CM of MSCs after 30 days prevented the fibrotic effects of curettage on endometrial layer of rabbits. Conclusions Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis better than BM-MSC in a rabbit model.